One of the mechanisms for regulating gene expression in animal cells is DNA methylation. Any gene which carries this modification appears to be marked as inactive. Using specially constructed transgenic mice it will be possible to test whether this mechanisms plays a significant role during normal development. A new technology for assaying the pattern of DNA methylation in oocyte DNA will allow a full description of specific modification in the germ line. Activation and inactivation during development is accompanied by specific alterations in methylation. By use of transfection into various cell types one can now evaluate both the cis and trans acting elements involved in this process. Although DNA replication is an important process and may be involved in the control of gene expression, little is known about the mechanisms to its regulation. Using an elegant new methodology to assay chromosomal replication origin function in situ, it is now possible to identify and isolate these elements and provide a complete description of their mode to action. Gene constructs will then be used to evaluate the relationship between DNA replication and gene regulation. Furthermore, analysis of replication in different tissue cell types and in transformed cells will yield information about the regulation of origin use in vivo.